Platelet (PLT) alloantigens are responsible for the pathogenesis of neonatal alloimmune thrombocytopenia (NAIT). Preventive, therapeutic and diagnostic advances are needed so that this self-limited disorder does not cause in utero or postnatal bleeding complications. In order to develop comprehensive screening and prevention programs, identification of the populations at risk is needed. The first goal of our proposal is to study the immunogenetics of the PLT-specific alloantigen systems in a variety of ethnic/racial groups. Improved methods of diagnosis, antenatal evaluation and elucidation of the immunologic factors that contribute to the pathogenesis of NAIT are needed. The second goal of this proposal is to characterize the clinical relevance of the alloantigens and antiplatelet antibodies involved in NAIT, including immunoglobulin subclass and allotype, cytotoxic mechanisms and target antigens. We will use our established PLT immunologic assays and in vitro cytotoxic assays to study PLT antibodies collected prospectively from babies with immune thrombocytopenia and from a serum bank of our previous patients. Development of a cDNA library will be used to detect and identify new PLT alloantigen systems. Production of recombinant PLT alloantigen mimics will be used to characterize PLT alloantibodies and to develop simplified methods of diagnosis. Estimation of fetal/newborn PLT turnover will be done by measurement of fetal glycocalicin levels in plasma and amniotic fluid. These studies should provide immunogenetic and immunologic information that will be of therapeutic and preventative relevance.